By targeting the circuitry in the brain, Sunnybrook doctors hope to pioneer a new approach to mental health treatment.
For 15 years, a Toronto woman endured severe depression, without getting relief from medication or other treatments.
With no end to this chronic condition in sight, she agreed to enroll in a clinical study of a new treatment known as deep brain stimulation (DBS), which delivers electrical stimulation to targeted areas in the brain and blocks abnormal nerve signals.
Within 10 months, the debilitating symptoms of depression became more manageable. One year later, the woman was well, says Dr. Anthony Levitt, chief of the Hurvitz Brain Sciences Program.
One of a number of treatments that fall under the term neuromodulation, DBS is an example of the high-tech procedures that will become available within the Hurvitz Brain Sciences Program at Sunnybrook.
– Dr. Anthony Levitt
Neuromodulation is the process of altering the brain’s circuitry by directly intervening inside the brain. Electrical, ultrasound or magnetic energy is used to change the brain’s circuitry or disrupt pathways.
The field of neuromodulation is rapidly evolving, and Sunnybrook has been leading the charge. As part of the goal to deliver care that’s tailored to the patient, Sunnybrook will house a Centre for Neuromodulation (CFN).
“Rather than a one-size-fits-all solution, we will provide individualized care,” says Dr. Nir Lipsman, a neurosurgeon and scientist at Sunnybrook. “Our ability to offer the full range of neuromodulation strategies all in one place will make this program unique on a global scale.”
Discoveries from neuromodulation techniques are opening up new treatment possibilities for people with conditions such as depression, obsessive compulsive disorder, schizophrenia and anorexia nervosa. “It’s a whole new way of looking at mental health treatment,” says Dr. Levitt, one of the lead physicians in charge of establishing the CFN.
“For the last 40 years, we’ve talked about mental illness as being a “chemical imbalance.” That understanding has helped, but our treatments remain 50 to 60 per cent effective and relapse is unfortunately still too frequent,” he says. There is renewed hope that understanding mental illnesses as brain circuitry disorders will provide a quantum leap forward in treatment: if mental illnesses are circuitry disorders, then once the malfunctioning circuits are found, they can be adjusted.
Cutting-edge and minimally invasive techniques, such as DBS and high intensity-focused ultrasound (HIFU), will be used at the CFN to modulate dysfunctional circuits for conditions as varied as dementia, stroke, depression and anxiety.
The rising prevalence of neuropsychiatric disorders is driving the urgency to find new treatments for these conditions. The number of Canadians with dementia is expected to double from 747,000 in 2011 to 1.4 million by 2031, while major depression has already become the number one cause of chronic illness and lost productivity worldwide.
Neuromodulation, one response to the coming crush, has become one of the fastest-growing areas in neuroscience and a new frontier for treatment of brain disorders.
Existing techniques, such as more invasive surgical procedures or electroconvulsive treatment (ECT), also adjust circuitry but lack precision and have side effects that are unacceptable to many patients. The use of HIFU, meanwhile, can much more precisely direct energy to the appropriate location in the brain and can modulate pathways that are not working as they should be, while leaving normally functioning circuits intact.
Already, protocols for the use of neuromodulation are being developed. “Our goal is to work on techniques to reach as many patients as possible,” says Dr. Lipsman.
“If we can change the abnormal pathways in the brain that are leading to these mental illnesses, it is entirely possible that we might be able to offer not just treatment, but a cure for some patients,” he says.
A non-invasive procedure, focused ultrasound uses high-frequency acoustic waves that reach hard-to access areas in organs such as the brain or prostate.
Focused ultrasound is used in combination with magnetic resonance imaging (MRI), which allows physicians to see the geography of the brain in real time as the procedure is carried out.
After being given a local anaesthetic, the patient is outfitted with a “helmet” that contains more than 1,000 individual sources of ultrasound. “The multiple sources are necessary because ultrasound does not pass very well through bone,” says Dr. Nir Lipsman, a neurosurgeon and scientist at Sunnybrook. The MRI is used to determine which region of the brain will be targeted. “The real-time nature of MRI further allows physicians to direct the helmet’s multiple sources of ultrasound to focus on a precise target, coming to within one millimetre of accuracy,” says Dr. Lipsman.
Years of experience and research have helped determine which areas of the brain are dysfunctional in specific disorders. For example, a less than five millimetre area in the brain’s thalamus is where abnormal activity occurs in patients with Essential Tremor. MRI-guided focused ultrasound was used at Sunnybrook for the first time in 2012 to cure a man with severe tremors. In the case of depression, the brain’s anterior cingulate area could also be targeted.
For anxiety or obsessive-compulsive disorder, the focus would be the anterior limb of the brain’s internal capsule, says Dr. Lipsman. Trials investigating focused ultrasound for these disorders are expected to begin at Sunnybrook within the year.
After the target is found, the power is increased “and HIFU heats the tissue and destroys neurons, tumours or other problem areas. You see the lesions develop before your eyes,” Dr. Lipsman says.
Risks such as infection or bleeding in the brain are virtually eliminated because HIFU is non-invasive, performed without making a hole in the skull. And because patients are awake, they can report problems such as a pins-and-needles feeling or weakness, which may indicate the target is off.
Deep brain stimulation
Deep brain stimulation (DBS) is an invasive procedure that uses electrodes to stimulate certain parts of the brain. DBS has been in use for over 25 years to treat Parkinson’s disease, and Sunnybrook’s Centre for Neuromodulation intends to explore DBS to treat conditions such as anorexia and depression, according to Dr. Lipsman.
Before the procedure, neurosurgeons use an MRI to locate the target within the brain where electrodes will be implanted, to disrupt electrical nerve signals that generate symptoms.
Two electrodes are then inserted on each side of the brain through a hole made in the skull. The tip of the electrode is positioned within the targeted brain area. An extension wire is then passed under the skin of the head and neck, to a battery pack, implanted under the skin beneath the collarbone. The battery provides constant electrical stimulation to the brain.
All photography by Doug Nicholson